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Neuropilin-1 high monocytes protect against neonatal inflammation.
- Source :
-
Cellular & molecular immunology [Cell Mol Immunol] 2024 Jun; Vol. 21 (6), pp. 575-588. Date of Electronic Publication: 2024 Apr 17. - Publication Year :
- 2024
-
Abstract
- Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis (NEC) due to their immature immune system. The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates, yet the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized by high levels of neuropilin-1 (Nrp1), termed Nrp1 <superscript>high</superscript> monocytes. Compared with their Nrp1 <superscript>low</superscript> counterparts, Nrp1 <superscript>high</superscript> monocytes displayed potent immunosuppressive activity. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1 <superscript>high</superscript> monocytes led to remission of NEC. Mechanistic studies showed that Nrp1, by binding to its ligand Sema4a, induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4. KLF4 transactivated Nos2 and enhanced the production of nitric oxide (NO), a key mediator of immunosuppression in monocytes. These findings reveal an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for treating inflammatory disorders in neonates.<br /> (© 2024. The Author(s), under exclusive licence to CSI and USTC.)
- Subjects :
- Animals
Humans
Mice
Nitric Oxide Synthase Type II metabolism
Nitric Oxide metabolism
Signal Transduction
TOR Serine-Threonine Kinases metabolism
Mice, Inbred C57BL
Infant, Newborn
p38 Mitogen-Activated Protein Kinases metabolism
Mice, Knockout
Monocytes metabolism
Monocytes immunology
Neuropilin-1 metabolism
Neuropilin-1 genetics
Kruppel-Like Factor 4
Inflammation pathology
Inflammation immunology
Animals, Newborn
Kruppel-Like Transcription Factors metabolism
Kruppel-Like Transcription Factors genetics
Enterocolitis, Necrotizing immunology
Enterocolitis, Necrotizing metabolism
Enterocolitis, Necrotizing prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 2042-0226
- Volume :
- 21
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cellular & molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 38632385
- Full Text :
- https://doi.org/10.1038/s41423-024-01157-7